Early T-cell precursor acute lymphoblastic leukemia and T/myeloid mixed phenotype acute leukemia possess overlapping characteristics and both benefit from CAG-like regimens and allogeneic hematopoietic stem cell transplantation

Abstract Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) and T/myeloid mixed phenotype acute leukemia (T/M-MPAL) are closely related entities and remain a therapeutic challenge. In this study, we characterized the clinical features of 43 ETP-ALL and 41 T/M-MPAL patients and compared clinical outcomes and safety between CAG (cytarabine, aclarubicin, and granulocyte colony stimulating factor)-like regimens in 34 patients and conventional ALL regimens in 50 patients. In our series, ETP-ALL and T/M-MPAL showed similar biological characteristics, immunophenotypes, genomic alterations, and outcomes. The complete remission (CR) rate and minimal residual disease (MRD)-negative CR rate of CAG-like regimens were significantly higher compared with conventional ALL regimens (80.0% vs. 59.7%; p=0.039, 51.4% vs. 31.3%; p=0.048). Overall, 90.0% (18/20) of cases achieved a CR using combined decitabine and CAG-like regimens. Additionally, CAG-like regimens had lower rates of grade 3-4 infection (18.8% vs. 38.2%; p=0.059) and grade 1-2 hepatotoxicity (37.5% vs. 60.0%; p=0.043) than conventional ALL regimens. The 38 patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the first CR (CR1) had better overall survival (OS) and leukemia-free survival (LFS) than the 11 patients who underwent allo-HSCT in the second CR (CR2) or in no remission (NR) (median OS: not reached vs. 7.6 months, p=0.0004; median LFS: not reached vs. 11.6 months, p=0.0008). There was a significant difference in 3-year OS (95.7% vs. 52.5%, p=0.0039) and LFS (95.8% vs. 43.5%, p=0.0003) after allo-HSCT between pre-transplant MRD-negative and MRD-positive patients. The median OS for patients without allo-HSCT was 32.1 months in the CAG-like group compared with 12.1 months in the non-CAG-like group (p=0.019). These findings suggest that ETP-ALL and T/M-MPAL possess overlapping characteristics and CAG-like regimens improve their clinical outcomes.